Combination effect of photodynamic therapy using NPe6 with pemetrexed for human malignant pleural mesothelioma cells.
نویسندگان
چکیده
To identify a possible new treatment modality for malignant pleural mesothelioma (MPM), we examined whether combination treatment consisting of pemetrexed chemotherapy and photodynamic therapy (PDT) using the photosensitizer NPe6, enhanced the antitumor effect in both in vitro and in vivo models. We also investigated preclinical treatment schedules. Four human malignant mesothelioma cell lines (MSTO‑211H, H2052, H2452 and H28) were assayed using the WST assay after treatment with pemetrexed and NPe6‑PDT. The treatment schedule for the combination treatment was examined using nude mice. Pemetrexed pre‑treatment enhanced the lethal effect of NPe6‑PDT in the four malignant mesothelioma cell lines, but NPe6‑PDT followed by pemetrexed treatment did not enhance cell lethality in the in vitro assay. Pemetrexed pre‑treatment did not enhance the intracellular accumulation of NPe6, which is one of the determinants of the antitumor effect of PDT. In nude mice injected with MSTO‑211H cells and then treated using a combination of pemetrexed and NPe6‑PDT (10 mg/kg NPe6, 10 J/cm(2) laser irradiation), the tumor volume decreased by 50% but subsequently increased, reaching the pre‑treatment value after 14 days. Pemetrexed treatment followed by NPe6‑PDT resulted in an 80% reduction in the tumor size and inhibited re‑growth. NPe6‑PDT followed by pemetrexed treatment resulted in a 60% reduction in tumor size but did not inhibit re‑growth. NPe6‑PDT induced the expression of thymidylate synthase (TS), which confers resistance to pemetrexed, and NPe6‑PDT followed by pemetrexed treatment did not enhance the treatment outcome in vivo. In conclusion, combination treatment, consisting of pemetrexed followed by NPe6‑PDT, should be further investigated as a new treatment modality for MPM. In the future, this combination treatment may contribute to a reduction in local recurrence and a prolonged survival period in patients with MPM.
منابع مشابه
A Case of Advanced Malignant Pleural Mesothelioma Treatment with Chemotherapy and Photodynamic Therapy
Malignant pleural mesothelioma (MPM) is an aggressive, treatment-resistant, and generally fatal disease. A 68-year-old male who was diagnosed with MPM at another hospital came to our hospital with dyspnea. We advised him to take combination chemotherapy but he refused to take the treatment. That was because he had already received chemotherapy with supportive care at another hospital but his co...
متن کاملSynergistic antitumor effects of regulatory T cell blockade combined with pemetrexed in murine malignant mesothelioma.
CD4(+)CD25(+) regulatory T cells (Tregs) can promote the growth of some tumors, but it is unknown whether this is true for all tumors, including malignant pleural mesothelioma. We have previously shown that the existence of Tregs was associated with poor survival in patients with malignant pleural mesothelioma. In this study, using an intrathoracic murine model of malignant mesothelioma (MM), w...
متن کاملInteraction and cross-resistance of cisplatin and pemetrexed in malignant pleural mesothelioma cell lines.
Although cisplatin and pemetrexed are key drugs in the treatment of malignant pleural mesothelioma, their drug-drug interactions, cross-resistance and resistance mechanisms in malignant pleural mesothelioma are not well understood. In the present study, the interaction of these 2 agents was determined by clonogenic assays followed by isobologram a...
متن کاملAcute lower limb ischemia complicating pemetrexed and carboplatin combination chemotherapy for malignant pleural mesothelioma.
Pemetrexed and Carboplatin are two well-known chemioterapic agents used for the treatment of many tumors, especially for lung cancer and mesothelioma. Peripheral ischemic events related to Pemetrexed and Carboplatin are rarely reported. We herein report a case of lower limb acute ischemia related to combined treatment of Pemetrexed and Carboplatin. A 68-year-old woman was given the chemiotherap...
متن کاملIntrapleural Photodynamic Therapy for Mesothelioma: What Place and Which Future?
In the surgical multimodal management of malignant pleural mesothelioma, it seems crucial to proceed with an efficient local adjuvant treatment to kill residual tumor cells. Intrapleural photodynamic therapy has recently emerged as a potential candidate in this goal. In this review, we analyzed and classified 16 articles in which patients with malignant pleural mesothelioma received intrapleura...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- International journal of oncology
دوره 46 2 شماره
صفحات -
تاریخ انتشار 2015